Biology:Death receptor 5

Short description: Protein found in humans

Generic protein structure example

Death receptor 5 (DR5), also known as TRAIL receptor 2 (TRAILR2) and tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), is a cell surface receptor of the TNF-receptor superfamily that binds TRAIL and mediates apoptosis.

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces apoptosis signal. Mice have a homologous gene, tnfrsf10b, that has been essential in the elucidation of the function of this gene in humans. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein.

Interactions

DR5 has been shown to interact with:

• Caspase 8,
• Caspase 10,
• FADD, and
• TRAIL.

Cancer therapy

Monoclonal antibodies targeting DR5 have been developed and are currently under clinical trials for patients suffer from a variety of cancer types, see Tigatuzumab (CS-1008).

Luminescent iridium complex-peptide hybrids, serving as TRAIL mimics, have been designed, which target the death receptors DR4 and DR5 on cancer cells and induce their apoptosis.

See also

• Cluster of differentiation
• Tumor necrosis factor receptor
• Tigatuzumab

Further reading

• "The complexity of TNF-related apoptosis-inducing ligand". Annals of the New York Academy of Sciences 926 (1): 52–63. 2001. doi:10.1111/j.1749-6632.2000.tb05598.x. PMID 11193041. 
• "Specificity of molecular recognition learned from the crystal structures of TRAIL and the TRAIL:sDR5 complex". Vitamins and Hormones 67: 1–17. 2004. doi:10.1016/S0083-6729(04)67001-4. ISBN 9780127098678. PMID 15110168. 
• "Following a TRAIL: update on a ligand and its five receptors". Cell Research 14 (5): 359–72. Oct 2004. doi:10.1038/sj.cr.7290236. PMID 15538968. 
• "An antagonist decoy receptor and a death domain-containing receptor for TRAIL". Science 277 (5327): 815–8. Aug 1997. doi:10.1126/science.277.5327.815. PMID 9242610. 
• "Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors". Science 277 (5327): 818–21. Aug 1997. doi:10.1126/science.277.5327.818. PMID 9242611. 
• "TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL". Current Biology 7 (9): 693–6. Sep 1997. doi:10.1016/S0960-9822(06)00297-1. PMID 9285725. 
• "TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL". The EMBO Journal 16 (17): 5386–97. Sep 1997. doi:10.1093/emboj/16.17.5386. PMID 9311998. 
• "Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL". The Journal of Biological Chemistry 272 (41): 25417–20. Oct 1997. doi:10.1074/jbc.272.41.25417. PMID 9325248. 
• "KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene". Nature Genetics 17 (2): 141–3. Oct 1997. doi:10.1038/ng1097-141. PMID 9326928. 
• "Characterization of two receptors for TRAIL". FEBS Letters 416 (3): 329–34. Oct 1997. doi:10.1016/S0014-5793(97)01231-3. PMID 9373179. https://serval.unil.ch/resource/serval:BIB_25D695CC2FFE.P001/REF.pdf. 
• "A novel receptor for Apo2L/TRAIL contains a truncated death domain". Current Biology 7 (12): 1003–6. Dec 1997. doi:10.1016/S0960-9822(06)00422-2. PMID 9382840. 
• "Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway". Immunity 7 (6): 821–30. Dec 1997. doi:10.1016/S1074-7613(00)80400-8. PMID 9430227. 
• "TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB". Immunity 7 (6): 831–6. Dec 1997. doi:10.1016/S1074-7613(00)80401-X. PMID 9430228. https://serval.unil.ch/notice/serval:BIB_1D571B98E298. 
• "Rare loss-of-function mutation of a death receptor gene in head and neck cancer". Cancer Research 58 (16): 3513–8. Aug 1998. PMID 9721851. 
• "Genomic organization and mutation analyses of the DR5/TRAIL receptor 2 gene in colorectal carcinomas". Cancer Letters 133 (2): 197–204. Nov 1998. doi:10.1016/S0304-3835(98)00230-4. PMID 10072170. 
• "Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation". Nature Structural Biology 6 (11): 1048–53. Nov 1999. doi:10.1038/14935. PMID 10542098. 
• "Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5". Molecular Cell 4 (4): 563–71. Oct 1999. doi:10.1016/S1097-2765(00)80207-5. PMID 10549288. 
• "FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts". The Journal of Biological Chemistry 275 (33): 25065–8. Aug 2000. doi:10.1074/jbc.C000284200. PMID 10862756. 
• "CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells". Oncogene 20 (31): 4258–69. Jul 2001. doi:10.1038/sj.onc.1204559. PMID 11464292. 

External links

• TNFRSF10B+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.